Thin walled articles are commonly used in the medical field, for example in microfluidic and/or polymerase chain reaction (PCR) applications. Microfluidic applications deal with the precise control of fluids that are geometrically constrained in microfluidic devices that can be characterized in general by the presence of one or more channels with at least one dimension of less than or equal to 1 millimeter (mm). Obtaining microfluidic devices that can achieve accurate fine mold detail replication and that can allow for the production of channels with such small dimensions is a constant challenge.
Considering PCR applications, PCR is a process used to amplify and copy a piece of DNA sequence across multiple orders of magnitude and is a vital technique in the field of molecular biology. In the PCR process, the DNA fragment is mixed in aqueous solution with complementary DNA primers and DNA polymerase enzyme and the mixture is taken through several thermal cycling steps. This thermal cycling process separates the double-helix of the target DNA sequence and initiates new DNA synthesis through the DNA polymerase catalyst. A typical thermal profile for the PCR reaction is shown below in Table 1, where ° C. is degrees Celsius.
TABLE 1StepTime DurationTemperature (° C.)Initial Denaturation2minutes94-95Denaturation20-30seconds94-95Primer Extension1minute72Final Extension5-15minutes72
The PCR reactions are typically carried out in microwells in arrays from 8 to 96 wells and volumes of 0.2-0.5 milliliters (mL). Due to the high number of samples in each microwell plate, the Society of Biomolecular Screening and the American National Standards Institute (ANSI) have published standards ANSI/SBS 1-2004 through 4-2004 for microwell plates concerning the particular dimensions and positions of the microwells for microwell plates having 96, 984, and 1536 wells.
Efficient heat transfer through the walls of the microwell to the reaction solution is required for strict temperature control during the PCR reaction process. In order to achieve efficient heat transfer, the PCR trays are designed with very thin microwell wall thicknesses, such as around 0.2 mm. Injection molding of these thin-wall trays becomes a significant challenge since an extremely high flow material is required to fill the thin microwell walls. In addition, the material needs to have sufficient heat resistance to avoid deformation during the PCR thermal cycling step, and optical clarity is desired so the liquid volume level can be observed. Typically, a polypropylene such as PD702 from LYONDELL BASELL is used for injection molding of the PCR trays. However, polypropylene is subject to softening at elevated temperatures such as those used in PCR denaturation cycles, which can cause PCR or other microfluidic components to become excessively flexible during processing, and/or be subject to warping or other physical deformation, and/or leaking.
Polycarbonate materials have not typically been used for thin-wall microfluidic applications such as PCR microwells because while many polycarbonates possess the clarity and high heat resistance desired for the PCR or other microfluidic applications, they have generally been thought to lack sufficient flow to fill the thin tooling required and/or do not have sufficient ductility at room temperature. Accordingly, polypropylene has generally been the thermoplastic of choice for PCR and other microfluidic applications.
While a number of microfluidic and/or PCR devices fabricated from polypropylene or other materials that have been used for such devices have been proposed, there is a continuing need in the art for materials for use in making thin walled articles that are compatible with the microfluidic and/or PCR operating conditions.